Abstract
Although meningiomas represent the most common class of tumors of the central nervous system, the molecular events underlying their genesis and development are still not well defined, and therapeutic approaches based on the genetics of these tumors are currently lacking. In the present study we have used the immunoblotting technique to show that the p16(INK4A), Cdk6 and pRB proteins are differentially expressed in primary meningioma cells with 20-, 30- and 36-fold difference between the lowest and the highest levels of each protein, respectively. In addition, we present evidence that the level of the anti-apoptosis survivin protein is high in these benign tumors. Moreover, the annexin V-associated flow cytometry technique was used to show that 60% of meningioma cell cultures underwent apoptosis in response to both gamma-rays and cisplatin, and 50% of these cells exhibited significant sensitivity to hydroxyurea. These agents triggered apoptosis through the mitochondrial pathway, by increasing the Bax/Bcl-2 ratio. Interestingly, the induction of apoptosis following radiation and cisplatin was significant in all cells that expressed low levels of p16(INK4A), Cdk6 and pRB proteins. These data shed more light on the molecular biology of meningioma cells and suggest that survivin and proteins of the RB pathway could play a determinant role in the development and the treatment of meningiomas.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Aged
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Antineoplastic Agents / pharmacology
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Apoptosis / drug effects
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Apoptosis / physiology*
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Cell Line, Tumor
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Cisplatin / pharmacology
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Cyclin-Dependent Kinase 6 / drug effects
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Cyclin-Dependent Kinase 6 / metabolism*
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Cyclin-Dependent Kinase 6 / radiation effects
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Cyclin-Dependent Kinase Inhibitor p16 / drug effects
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Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
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Cyclin-Dependent Kinase Inhibitor p16 / radiation effects
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Female
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Flow Cytometry
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Humans
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Hydroxyurea / pharmacology
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Immunoblotting
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Inhibitor of Apoptosis Proteins
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Male
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Meningeal Neoplasms / drug therapy
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Meningeal Neoplasms / metabolism*
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Meningeal Neoplasms / radiotherapy
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Meningioma / drug therapy
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Meningioma / metabolism*
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Meningioma / radiotherapy
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Microtubule-Associated Proteins / drug effects
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Microtubule-Associated Proteins / metabolism*
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Microtubule-Associated Proteins / radiation effects
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Middle Aged
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Neoplasm Proteins / drug effects
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Neoplasm Proteins / metabolism*
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Neoplasm Proteins / radiation effects
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Proto-Oncogene Proteins c-bcl-2 / drug effects
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Proto-Oncogene Proteins c-bcl-2 / radiation effects
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Radiotherapy
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Retinoblastoma Protein / drug effects
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Retinoblastoma Protein / metabolism*
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Retinoblastoma Protein / radiation effects
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Survivin
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Up-Regulation / drug effects
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Up-Regulation / physiology
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Up-Regulation / radiation effects
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bcl-2-Associated X Protein / drug effects
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bcl-2-Associated X Protein / metabolism
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bcl-2-Associated X Protein / radiation effects
Substances
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Antineoplastic Agents
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BIRC5 protein, human
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Cyclin-Dependent Kinase Inhibitor p16
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Inhibitor of Apoptosis Proteins
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Microtubule-Associated Proteins
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Neoplasm Proteins
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Proto-Oncogene Proteins c-bcl-2
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Retinoblastoma Protein
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Survivin
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bcl-2-Associated X Protein
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CDK6 protein, human
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Cyclin-Dependent Kinase 6
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Cisplatin
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Hydroxyurea